Abstract

The continuing goal of this project is to develop equivalent human and rat mammary gland in vitro cell systems that will be used for an organ-specific interspecies comparison of the interaction of chemical carcinogens with these cells. In vitro systems developed for these comparisons may also provide human organ-specific cell systems to evaluate the toxicity of environmental chemicals. To achieve these goals we will first complete the development of equivalent methods to grow human and rat mammary cells in well characterized mass and clonal cultures. These culture systems will be used in both direct and cell-mediated mutagenesis assays. These biological assays, together with the biochemical evaluation of carcinogen metabolism and formation and removal of DNA carcinogen adducts by these mammary cells, will be used to compare the interactions of chemical carcinogens with human and rat mammary cells in vitro. Both intra- and interspecies qualiltative and quantitative differences will be documented. This project will provide and evaluate human organ-specific cell culture systems that may be useful in identifying environmental carcinogen. It will also address the question of interspecies extrapolation of carcinogen-cell interactions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA030295-06
Application #
3169208
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1981-09-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Albertini, M R; Howard, S P; Fisch, P et al. (1993) Modulation of target-cell culture conditions alters susceptibility to lymphocyte-mediated lysis. J Immunother Emphasis Tumor Immunol 13:243-51
Eldridge, S R; Gould, M N; Butterworth, B E (1992) Genotoxicity of environmental agents in human mammary epithelial cells. Cancer Res 52:5617-21
Eldridge, S R; Gould, M N (1992) Comparison of spontaneous mutagenesis in early-passage human mammary cells from normal and malignant tissues. Int J Cancer 50:321-4
Eldridge, S R; Gould, M N (1991) Specific locus mutagenesis of human mammary epithelial cells by ultraviolet radiation. Int J Radiat Biol 59:807-14
Zhang, R; Wiley, J; Howard, S P et al. (1989) Rare clonal karyotypic variants in primary cultures of human breast carcinoma cells. Cancer Res 49:444-9
Eldridge, S R; Martens, T W; Sattler, C A et al. (1989) Association of decreased intercellular communication with the immortal but not the tumorigenic phenotype in human mammary epithelial cells. Cancer Res 49:4326-31
Seidman, L A; Moore, C J; Gould, M N (1988) 32P-postlabeling analysis of DNA adducts in human and rat mammary epithelial cells. Carcinogenesis 9:1071-7
Moore, C J; Pruess-Schwartz, D; Mauthe, R J et al. (1987) Interspecies differences in the major DNA adducts formed from benzo(a)pyrene but not 7,12-dimethylbenz(a)anthracene in rat and human mammary cell cultures. Cancer Res 47:4402-6
Marshall, J S; Gordon, N H; Hubay, C A et al. (1987) Assessment of tamoxifen as adjuvant therapy in stage II breast cancer: a long-term follow-up. J Lab Clin Med 109:300-7
Moore, C J; Eldridge, S R; Tricomi, W A et al. (1987) Quantitation of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene binding to nuclear macromolecules in human and rat mammary epithelial cells. Cancer Res 47:2609-13

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